Author Of 1 Presentation
P1121 - Effector T cells are selectively controlled and related to postpartum relapses during pregnancy in MS (ID 1610)
Abstract
Background
Women with multiple sclerosis (MS) experience limited relapses during pregnancy, while an increased relapse risk is observed within the first period after delivery. How extensive pregnancy-associated fluctuations of serum proteins correspond to brain-homing effector T cells and whether this differs between pregnant MS patients and healthy controls is currently unknown.
Objectives
Here, we aimed to assess the effector phenotype and outgrowth of T-cell subsets in relation to pregnancy, pregnancy-related serum factors and postpartum relapses in MS.
Methods
Paired third trimester and 4-8 weeks postpartum blood samples from pregnant MS patients with and without a postpartum relapse (n=21) were compared to age-matched pregnant healthy controls (n=12) for memory phenotype, skewing and activation of T cells. Memory T cells were sorted, activated and analyzed for production of inflammatory cytokines (multiplex assay). Third trimester and postpartum sera were added to CFSE-labeled, proliferating T cells for 72 hours. Serum cortisol, estradiol and progesterone levels were determined using liquid chromatography-mass spectrometry.
Results
Frequencies of effector memory (CCR7-CD45RA-) CD4+ and not CD8+ T cells were selectively increased in postpartum versus third trimester blood of 15 MS patients without a postpartum relapse. This was not seen for 6 patients experiencing a postpartum relapse or in pregnant healthy controls. Brain-homing markers CCR6 and CXCR3 were enriched on memory CD4+ T cells derived from postpartum samples, except for patients with a postpartum relapse. These differences in effector T-cell phenotypes were also found in vitro using paired third trimester and postpartum sera from pregnant MS patients and controls, suggesting that this is at least partly regulated by soluble factors. Serum cortisol, estradiol and progesterone levels did not differ or correlate to outcome measures in third trimester samples. In sharp contrast to non-relapsing patients, memory CD4+ T cells were activated (HLA-DR+) and showed an overall increase in inflammatory cytokine production in third trimester samples from MS patients who experienced a postpartum relapse.
Conclusions
These data demonstrate that effector CD4+ T cells are alternatively controlled in pregnant MS patients, which is influenced by serum-derived factors. Moreover, we found first indications that the activation state of these cells during pregnancy may be used to predict a postpartum relapse in MS.